Shanghai Medical College, Fudan University, Shanghai, China.
Mol Med. 2012 Sep 25;18(1):1136-46. doi: 10.2119/molmed.2012.00055.
Isocorydine (ICD), an anticancer agent under current evaluation, decreased the percentage of side population (SP) cells significantly in hepatocellular carcinoma (HCC) cell lines. ICD treatment sensitized cancer cells to doxorubicin (DXR), a conventional clinical chemotherapeutic drug for HCC. We found that ICD decreased the percentage of SP cells in HCC cell lines by preferentially killing SP cells. In the early stage of treatment, ICD inhibited SP cell growth by arresting cells in G2/M; later, it induced apoptosis. Our xenograft model confirmed that ICD selectively reduced the size and weight of SP-induced tumor masses in vivo. Furthermore, it was found that programmed cell death 4 (PDCD4), a tumor suppressor gene, was relatively low when expressed in SP cells compared with non-SP cells, and its expression level was remarkably elevated when cells were treated with ICD. Taken together, these data suggest that ICD is a drug that may target the SP cells of HCC.
异紫堇碱（ICD）是一种正在评估的抗癌药物，它显著降低了肝癌（HCC）细胞系中侧群（SP）细胞的比例。ICD 处理使癌细胞对多柔比星（DXR）敏感，DXR 是 HCC 的常规临床化疗药物。我们发现 ICD 通过优先杀死 SP 细胞来降低 HCC 细胞系中 SP 细胞的比例。在治疗的早期阶段，ICD 通过将细胞阻滞在 G2/M 期来抑制 SP 细胞的生长；后来，它诱导细胞凋亡。我们的异种移植模型证实，ICD 可选择性地减少体内 SP 诱导的肿瘤肿块的大小和重量。此外，发现在 SP 细胞中表达时，肿瘤抑制基因程序性细胞死亡因子 4（PDCD4）相对较低，而在用 ICD 处理时其表达水平显著升高。综上所述，这些数据表明 ICD 可能是一种针对 HCC 的 SP 细胞的药物。
